This request for renewal of a Senior Scientist Award will support salary expenses for the principal investigator of several projects studying the psychopathology, pathophysiology, and genetics of schizophrenia. One set of studies investigates certain physiological and cognitive traits that occur more frequently among the first-degree biological relatives of schizophrenic patients than in the general population. These traits are not maladaptive in themselves, but they are useful as probes into the pathophysiology of schizophrenia, and also serve as supplementary phenotypes in chromosomal linkage analysis. Two such traits are ETD and impaired spatial working memory. The candidate is studying these two traits, using a parsing methodology as well as PET and fMRI. In addition, the candidate is continuing to gather data on patients and their first-degree family members to determine the coaggregation of these and other traits (cognitive interference, dysmorphology, and event-related potentials) in these families. The samples are drawn from McLean Hospital. Investigators from other Harvard institutions (including the Psychology and Statistics Departments of Harvard University) are centrally involved in these studies. In addition, a large linkage study, based in Denmark, in which the candidate collects eye tracking performance, thought disorder measures, and careful psychiatric diagnostic interviews, provides DNA samples, which are analyzed at the Neurogenetics Unit of the Massachusetts General Hospital.